Viral oncoprotein antibodies as a marker for recurrence of Merkel cell carcinoma: A prospective validation study
BACKGROUND Merkel cell carcinoma (MCC) is an aggressive skin cancer with a recurrence rate of >40%. Of the 2000 MCC cases per year in the United States, most are caused by the Merkel cell polyomavirus (MCPyV). Antibodies to MCPyV oncoprotein (T‐antigens) have been correlated with MCC tumor burden...
Gespeichert in:
| Veröffentlicht in: | Cancer 2017-04, Vol.123 (8), p.1464-1474 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1474 |
|---|---|
| container_issue | 8 |
| container_start_page | 1464 |
| container_title | Cancer |
| container_volume | 123 |
| creator | Paulson, Kelly G. Lewis, Christopher W. Redman, Mary W. Simonson, William T. Lisberg, Aaron Ritter, Deborah Morishima, Chihiro Hutchinson, Kathleen Mudgistratova, Lola Blom, Astrid Iyer, Jayasri Moshiri, Ata S. Tarabadkar, Erica S. Carter, Joseph J. Bhatia, Shailender Kawasumi, Masaoki Galloway, Denise A. Wener, Mark H. Nghiem, Paul |
| description | BACKGROUND
Merkel cell carcinoma (MCC) is an aggressive skin cancer with a recurrence rate of >40%. Of the 2000 MCC cases per year in the United States, most are caused by the Merkel cell polyomavirus (MCPyV). Antibodies to MCPyV oncoprotein (T‐antigens) have been correlated with MCC tumor burden. The present study assesses the clinical utility of MCPyV‐oncoprotein antibody titers for MCC prognostication and surveillance.
METHODS
MCPyV‐oncoprotein antibody detection was optimized in a clinical laboratory. A cohort of 219 patients with newly diagnosed MCC were followed prospectively (median follow‐up, 1.9 years). Among the seropositive patients, antibody titer and disease status were serially tracked.
RESULTS
Antibodies to MCPyV oncoproteins were rare among healthy individuals (1%) but were present in most patients with MCC (114 of 219 patients [52%]; P |
| doi_str_mv | 10.1002/cncr.30475 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5384867</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1891874847</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5475-5b8e3457ec9bed15d6c7a69efc1b220bd5caa4cdcd4b12a72af44c3367652c6e3</originalsourceid><addsrcrecordid>eNqNkV2L1DAUhoMo7jh64w-QgDcidE3SfLReLCyDX7AqiIp3IT091aydpCbtyPx7M866qBcihISQh4e85yXkPmennDHxBAKk05pJo26QFWetqRiX4iZZMcaaSsn60wm5k_NluRqh6tvkRJhWKK3VikwffXIjjQHilOKMPlAXZt_F3mOmriy6dekrJjrERBPCkhIGQBoH-hrLw0gBx7K5BD7ErXtKz2kx5Qlh9jukOzf63s0-Bprnpd_fJbcGN2a8d3WuyYfnz95vXlYXb1-82pxfVKBKkEp1DdZSGYS2w56rXoNxusUBeCcE63oFzknooZcdF84IN0gJda2NVgI01mtydvROS7fFHjDMJaidki959jY6b_98Cf6L_Rx3VtWNbLQpgkdXghS_LZhnu_X5kNUFjEu2vGl5Y2Qj_weV2gjRlCrW5OFf6GVcUiiTsLwVTOq2dFOox0cKyiRzwuH635zZQ-f20Ln92XmBH_ye9Br9VXIB-BH47kfc_0NlN282747SHzC0uY4</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1920469279</pqid></control><display><type>article</type><title>Viral oncoprotein antibodies as a marker for recurrence of Merkel cell carcinoma: A prospective validation study</title><source>MEDLINE</source><source>Access via Wiley Online Library</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Wiley Online Library (Open Access Collection)</source><source>Alma/SFX Local Collection</source><creator>Paulson, Kelly G. ; Lewis, Christopher W. ; Redman, Mary W. ; Simonson, William T. ; Lisberg, Aaron ; Ritter, Deborah ; Morishima, Chihiro ; Hutchinson, Kathleen ; Mudgistratova, Lola ; Blom, Astrid ; Iyer, Jayasri ; Moshiri, Ata S. ; Tarabadkar, Erica S. ; Carter, Joseph J. ; Bhatia, Shailender ; Kawasumi, Masaoki ; Galloway, Denise A. ; Wener, Mark H. ; Nghiem, Paul</creator><creatorcontrib>Paulson, Kelly G. ; Lewis, Christopher W. ; Redman, Mary W. ; Simonson, William T. ; Lisberg, Aaron ; Ritter, Deborah ; Morishima, Chihiro ; Hutchinson, Kathleen ; Mudgistratova, Lola ; Blom, Astrid ; Iyer, Jayasri ; Moshiri, Ata S. ; Tarabadkar, Erica S. ; Carter, Joseph J. ; Bhatia, Shailender ; Kawasumi, Masaoki ; Galloway, Denise A. ; Wener, Mark H. ; Nghiem, Paul</creatorcontrib><description>BACKGROUND
Merkel cell carcinoma (MCC) is an aggressive skin cancer with a recurrence rate of >40%. Of the 2000 MCC cases per year in the United States, most are caused by the Merkel cell polyomavirus (MCPyV). Antibodies to MCPyV oncoprotein (T‐antigens) have been correlated with MCC tumor burden. The present study assesses the clinical utility of MCPyV‐oncoprotein antibody titers for MCC prognostication and surveillance.
METHODS
MCPyV‐oncoprotein antibody detection was optimized in a clinical laboratory. A cohort of 219 patients with newly diagnosed MCC were followed prospectively (median follow‐up, 1.9 years). Among the seropositive patients, antibody titer and disease status were serially tracked.
RESULTS
Antibodies to MCPyV oncoproteins were rare among healthy individuals (1%) but were present in most patients with MCC (114 of 219 patients [52%]; P < .01). Seropositivity at diagnosis independently predicted decreased recurrence risk (hazard ratio, 0.58; P = .04) in multivariate analyses adjusted for age, sex, stage, and immunosuppression. After initial treatment, seropositive patients whose disease did not recur had rapidly falling titers that became negative by a median of 8.4 months. Among seropositive patients who underwent serial evaluation (71 patients; 282 time points), an increasing oncoprotein titer had a positive predictive value of 66% for clinically evident recurrence, whereas a decreasing titer had a negative predictive value of 97%.
CONCLUSIONS
Determination of oncoprotein antibody titer assists in the clinical management of patients with newly diagnosed MCC by stratifying them into a higher risk seronegative cohort, in which radiologic imaging may play a more prominent role, and into a lower risk seropositive cohort, in which disease status can be tracked in part by oncoprotein antibody titer. Cancer 2017;123:1464–1474. © 2016 American Cancer Society.
More than 40% of patients who are diagnosed with virally associated Merkel cell carcinoma will develop recurrent disease. In this report, a Merkel cell polyomavirus oncoprotein antibody titer is clinically useful in patients with newly diagnosed Merkel cell carcinoma, because it identifies 2 groups: antibody‐negative patients, who have a higher risk of recurrence, and antibody‐positive patients, in whom the ability of this test to serve as a serial tumor marker is prospectively validated with high sensitivity and specificity.</description><identifier>ISSN: 0008-543X</identifier><identifier>EISSN: 1097-0142</identifier><identifier>DOI: 10.1002/cncr.30475</identifier><identifier>PMID: 27925665</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Aged ; Aged, 80 and over ; Antibodies ; Antibodies, Viral - blood ; Antibodies, Viral - immunology ; Antigens ; Biomarkers ; Cancer ; Carcinoma, Merkel Cell - diagnosis ; Carcinoma, Merkel Cell - epidemiology ; Carcinoma, Merkel Cell - etiology ; Carcinoma, Merkel Cell - mortality ; Falling ; Female ; Health risks ; Humans ; Immunoglobulins ; Immunosuppression ; Male ; Merkel cell carcinoma (MCC) ; Merkel cell polyomavirus (MCPyV) ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Oncogene Proteins, Viral - immunology ; Oncology ; oncoprotein ; Oncoproteins ; Patients ; Polyomaviridae ; Population Surveillance ; Prospective Studies ; Reproducibility of Results ; Risk ; Seroepidemiologic Studies ; serology ; Skin cancer ; T antigen ; Tumor markers ; Tumor Virus Infections - complications ; Tumor Virus Infections - immunology ; Tumor Virus Infections - virology</subject><ispartof>Cancer, 2017-04, Vol.123 (8), p.1464-1474</ispartof><rights>2016 American Cancer Society</rights><rights>2016 American Cancer Society.</rights><rights>2017 American Cancer Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5475-5b8e3457ec9bed15d6c7a69efc1b220bd5caa4cdcd4b12a72af44c3367652c6e3</citedby><cites>FETCH-LOGICAL-c5475-5b8e3457ec9bed15d6c7a69efc1b220bd5caa4cdcd4b12a72af44c3367652c6e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fcncr.30475$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fcncr.30475$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,315,781,785,886,1418,1434,27929,27930,45579,45580,46414,46838</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27925665$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Paulson, Kelly G.</creatorcontrib><creatorcontrib>Lewis, Christopher W.</creatorcontrib><creatorcontrib>Redman, Mary W.</creatorcontrib><creatorcontrib>Simonson, William T.</creatorcontrib><creatorcontrib>Lisberg, Aaron</creatorcontrib><creatorcontrib>Ritter, Deborah</creatorcontrib><creatorcontrib>Morishima, Chihiro</creatorcontrib><creatorcontrib>Hutchinson, Kathleen</creatorcontrib><creatorcontrib>Mudgistratova, Lola</creatorcontrib><creatorcontrib>Blom, Astrid</creatorcontrib><creatorcontrib>Iyer, Jayasri</creatorcontrib><creatorcontrib>Moshiri, Ata S.</creatorcontrib><creatorcontrib>Tarabadkar, Erica S.</creatorcontrib><creatorcontrib>Carter, Joseph J.</creatorcontrib><creatorcontrib>Bhatia, Shailender</creatorcontrib><creatorcontrib>Kawasumi, Masaoki</creatorcontrib><creatorcontrib>Galloway, Denise A.</creatorcontrib><creatorcontrib>Wener, Mark H.</creatorcontrib><creatorcontrib>Nghiem, Paul</creatorcontrib><title>Viral oncoprotein antibodies as a marker for recurrence of Merkel cell carcinoma: A prospective validation study</title><title>Cancer</title><addtitle>Cancer</addtitle><description>BACKGROUND
Merkel cell carcinoma (MCC) is an aggressive skin cancer with a recurrence rate of >40%. Of the 2000 MCC cases per year in the United States, most are caused by the Merkel cell polyomavirus (MCPyV). Antibodies to MCPyV oncoprotein (T‐antigens) have been correlated with MCC tumor burden. The present study assesses the clinical utility of MCPyV‐oncoprotein antibody titers for MCC prognostication and surveillance.
METHODS
MCPyV‐oncoprotein antibody detection was optimized in a clinical laboratory. A cohort of 219 patients with newly diagnosed MCC were followed prospectively (median follow‐up, 1.9 years). Among the seropositive patients, antibody titer and disease status were serially tracked.
RESULTS
Antibodies to MCPyV oncoproteins were rare among healthy individuals (1%) but were present in most patients with MCC (114 of 219 patients [52%]; P < .01). Seropositivity at diagnosis independently predicted decreased recurrence risk (hazard ratio, 0.58; P = .04) in multivariate analyses adjusted for age, sex, stage, and immunosuppression. After initial treatment, seropositive patients whose disease did not recur had rapidly falling titers that became negative by a median of 8.4 months. Among seropositive patients who underwent serial evaluation (71 patients; 282 time points), an increasing oncoprotein titer had a positive predictive value of 66% for clinically evident recurrence, whereas a decreasing titer had a negative predictive value of 97%.
CONCLUSIONS
Determination of oncoprotein antibody titer assists in the clinical management of patients with newly diagnosed MCC by stratifying them into a higher risk seronegative cohort, in which radiologic imaging may play a more prominent role, and into a lower risk seropositive cohort, in which disease status can be tracked in part by oncoprotein antibody titer. Cancer 2017;123:1464–1474. © 2016 American Cancer Society.
More than 40% of patients who are diagnosed with virally associated Merkel cell carcinoma will develop recurrent disease. In this report, a Merkel cell polyomavirus oncoprotein antibody titer is clinically useful in patients with newly diagnosed Merkel cell carcinoma, because it identifies 2 groups: antibody‐negative patients, who have a higher risk of recurrence, and antibody‐positive patients, in whom the ability of this test to serve as a serial tumor marker is prospectively validated with high sensitivity and specificity.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antibodies</subject><subject>Antibodies, Viral - blood</subject><subject>Antibodies, Viral - immunology</subject><subject>Antigens</subject><subject>Biomarkers</subject><subject>Cancer</subject><subject>Carcinoma, Merkel Cell - diagnosis</subject><subject>Carcinoma, Merkel Cell - epidemiology</subject><subject>Carcinoma, Merkel Cell - etiology</subject><subject>Carcinoma, Merkel Cell - mortality</subject><subject>Falling</subject><subject>Female</subject><subject>Health risks</subject><subject>Humans</subject><subject>Immunoglobulins</subject><subject>Immunosuppression</subject><subject>Male</subject><subject>Merkel cell carcinoma (MCC)</subject><subject>Merkel cell polyomavirus (MCPyV)</subject><subject>Middle Aged</subject><subject>Neoplasm Recurrence, Local</subject><subject>Neoplasm Staging</subject><subject>Oncogene Proteins, Viral - immunology</subject><subject>Oncology</subject><subject>oncoprotein</subject><subject>Oncoproteins</subject><subject>Patients</subject><subject>Polyomaviridae</subject><subject>Population Surveillance</subject><subject>Prospective Studies</subject><subject>Reproducibility of Results</subject><subject>Risk</subject><subject>Seroepidemiologic Studies</subject><subject>serology</subject><subject>Skin cancer</subject><subject>T antigen</subject><subject>Tumor markers</subject><subject>Tumor Virus Infections - complications</subject><subject>Tumor Virus Infections - immunology</subject><subject>Tumor Virus Infections - virology</subject><issn>0008-543X</issn><issn>1097-0142</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkV2L1DAUhoMo7jh64w-QgDcidE3SfLReLCyDX7AqiIp3IT091aydpCbtyPx7M866qBcihISQh4e85yXkPmennDHxBAKk05pJo26QFWetqRiX4iZZMcaaSsn60wm5k_NluRqh6tvkRJhWKK3VikwffXIjjQHilOKMPlAXZt_F3mOmriy6dekrJjrERBPCkhIGQBoH-hrLw0gBx7K5BD7ErXtKz2kx5Qlh9jukOzf63s0-Bprnpd_fJbcGN2a8d3WuyYfnz95vXlYXb1-82pxfVKBKkEp1DdZSGYS2w56rXoNxusUBeCcE63oFzknooZcdF84IN0gJda2NVgI01mtydvROS7fFHjDMJaidki959jY6b_98Cf6L_Rx3VtWNbLQpgkdXghS_LZhnu_X5kNUFjEu2vGl5Y2Qj_weV2gjRlCrW5OFf6GVcUiiTsLwVTOq2dFOox0cKyiRzwuH635zZQ-f20Ln92XmBH_ye9Br9VXIB-BH47kfc_0NlN282747SHzC0uY4</recordid><startdate>20170415</startdate><enddate>20170415</enddate><creator>Paulson, Kelly G.</creator><creator>Lewis, Christopher W.</creator><creator>Redman, Mary W.</creator><creator>Simonson, William T.</creator><creator>Lisberg, Aaron</creator><creator>Ritter, Deborah</creator><creator>Morishima, Chihiro</creator><creator>Hutchinson, Kathleen</creator><creator>Mudgistratova, Lola</creator><creator>Blom, Astrid</creator><creator>Iyer, Jayasri</creator><creator>Moshiri, Ata S.</creator><creator>Tarabadkar, Erica S.</creator><creator>Carter, Joseph J.</creator><creator>Bhatia, Shailender</creator><creator>Kawasumi, Masaoki</creator><creator>Galloway, Denise A.</creator><creator>Wener, Mark H.</creator><creator>Nghiem, Paul</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TO</scope><scope>7U7</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>7U9</scope><scope>5PM</scope></search><sort><creationdate>20170415</creationdate><title>Viral oncoprotein antibodies as a marker for recurrence of Merkel cell carcinoma: A prospective validation study</title><author>Paulson, Kelly G. ; Lewis, Christopher W. ; Redman, Mary W. ; Simonson, William T. ; Lisberg, Aaron ; Ritter, Deborah ; Morishima, Chihiro ; Hutchinson, Kathleen ; Mudgistratova, Lola ; Blom, Astrid ; Iyer, Jayasri ; Moshiri, Ata S. ; Tarabadkar, Erica S. ; Carter, Joseph J. ; Bhatia, Shailender ; Kawasumi, Masaoki ; Galloway, Denise A. ; Wener, Mark H. ; Nghiem, Paul</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5475-5b8e3457ec9bed15d6c7a69efc1b220bd5caa4cdcd4b12a72af44c3367652c6e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antibodies</topic><topic>Antibodies, Viral - blood</topic><topic>Antibodies, Viral - immunology</topic><topic>Antigens</topic><topic>Biomarkers</topic><topic>Cancer</topic><topic>Carcinoma, Merkel Cell - diagnosis</topic><topic>Carcinoma, Merkel Cell - epidemiology</topic><topic>Carcinoma, Merkel Cell - etiology</topic><topic>Carcinoma, Merkel Cell - mortality</topic><topic>Falling</topic><topic>Female</topic><topic>Health risks</topic><topic>Humans</topic><topic>Immunoglobulins</topic><topic>Immunosuppression</topic><topic>Male</topic><topic>Merkel cell carcinoma (MCC)</topic><topic>Merkel cell polyomavirus (MCPyV)</topic><topic>Middle Aged</topic><topic>Neoplasm Recurrence, Local</topic><topic>Neoplasm Staging</topic><topic>Oncogene Proteins, Viral - immunology</topic><topic>Oncology</topic><topic>oncoprotein</topic><topic>Oncoproteins</topic><topic>Patients</topic><topic>Polyomaviridae</topic><topic>Population Surveillance</topic><topic>Prospective Studies</topic><topic>Reproducibility of Results</topic><topic>Risk</topic><topic>Seroepidemiologic Studies</topic><topic>serology</topic><topic>Skin cancer</topic><topic>T antigen</topic><topic>Tumor markers</topic><topic>Tumor Virus Infections - complications</topic><topic>Tumor Virus Infections - immunology</topic><topic>Tumor Virus Infections - virology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Paulson, Kelly G.</creatorcontrib><creatorcontrib>Lewis, Christopher W.</creatorcontrib><creatorcontrib>Redman, Mary W.</creatorcontrib><creatorcontrib>Simonson, William T.</creatorcontrib><creatorcontrib>Lisberg, Aaron</creatorcontrib><creatorcontrib>Ritter, Deborah</creatorcontrib><creatorcontrib>Morishima, Chihiro</creatorcontrib><creatorcontrib>Hutchinson, Kathleen</creatorcontrib><creatorcontrib>Mudgistratova, Lola</creatorcontrib><creatorcontrib>Blom, Astrid</creatorcontrib><creatorcontrib>Iyer, Jayasri</creatorcontrib><creatorcontrib>Moshiri, Ata S.</creatorcontrib><creatorcontrib>Tarabadkar, Erica S.</creatorcontrib><creatorcontrib>Carter, Joseph J.</creatorcontrib><creatorcontrib>Bhatia, Shailender</creatorcontrib><creatorcontrib>Kawasumi, Masaoki</creatorcontrib><creatorcontrib>Galloway, Denise A.</creatorcontrib><creatorcontrib>Wener, Mark H.</creatorcontrib><creatorcontrib>Nghiem, Paul</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>Virology and AIDS Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Paulson, Kelly G.</au><au>Lewis, Christopher W.</au><au>Redman, Mary W.</au><au>Simonson, William T.</au><au>Lisberg, Aaron</au><au>Ritter, Deborah</au><au>Morishima, Chihiro</au><au>Hutchinson, Kathleen</au><au>Mudgistratova, Lola</au><au>Blom, Astrid</au><au>Iyer, Jayasri</au><au>Moshiri, Ata S.</au><au>Tarabadkar, Erica S.</au><au>Carter, Joseph J.</au><au>Bhatia, Shailender</au><au>Kawasumi, Masaoki</au><au>Galloway, Denise A.</au><au>Wener, Mark H.</au><au>Nghiem, Paul</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Viral oncoprotein antibodies as a marker for recurrence of Merkel cell carcinoma: A prospective validation study</atitle><jtitle>Cancer</jtitle><addtitle>Cancer</addtitle><date>2017-04-15</date><risdate>2017</risdate><volume>123</volume><issue>8</issue><spage>1464</spage><epage>1474</epage><pages>1464-1474</pages><issn>0008-543X</issn><eissn>1097-0142</eissn><abstract>BACKGROUND
Merkel cell carcinoma (MCC) is an aggressive skin cancer with a recurrence rate of >40%. Of the 2000 MCC cases per year in the United States, most are caused by the Merkel cell polyomavirus (MCPyV). Antibodies to MCPyV oncoprotein (T‐antigens) have been correlated with MCC tumor burden. The present study assesses the clinical utility of MCPyV‐oncoprotein antibody titers for MCC prognostication and surveillance.
METHODS
MCPyV‐oncoprotein antibody detection was optimized in a clinical laboratory. A cohort of 219 patients with newly diagnosed MCC were followed prospectively (median follow‐up, 1.9 years). Among the seropositive patients, antibody titer and disease status were serially tracked.
RESULTS
Antibodies to MCPyV oncoproteins were rare among healthy individuals (1%) but were present in most patients with MCC (114 of 219 patients [52%]; P < .01). Seropositivity at diagnosis independently predicted decreased recurrence risk (hazard ratio, 0.58; P = .04) in multivariate analyses adjusted for age, sex, stage, and immunosuppression. After initial treatment, seropositive patients whose disease did not recur had rapidly falling titers that became negative by a median of 8.4 months. Among seropositive patients who underwent serial evaluation (71 patients; 282 time points), an increasing oncoprotein titer had a positive predictive value of 66% for clinically evident recurrence, whereas a decreasing titer had a negative predictive value of 97%.
CONCLUSIONS
Determination of oncoprotein antibody titer assists in the clinical management of patients with newly diagnosed MCC by stratifying them into a higher risk seronegative cohort, in which radiologic imaging may play a more prominent role, and into a lower risk seropositive cohort, in which disease status can be tracked in part by oncoprotein antibody titer. Cancer 2017;123:1464–1474. © 2016 American Cancer Society.
More than 40% of patients who are diagnosed with virally associated Merkel cell carcinoma will develop recurrent disease. In this report, a Merkel cell polyomavirus oncoprotein antibody titer is clinically useful in patients with newly diagnosed Merkel cell carcinoma, because it identifies 2 groups: antibody‐negative patients, who have a higher risk of recurrence, and antibody‐positive patients, in whom the ability of this test to serve as a serial tumor marker is prospectively validated with high sensitivity and specificity.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>27925665</pmid><doi>10.1002/cncr.30475</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0008-543X |
| ispartof | Cancer, 2017-04, Vol.123 (8), p.1464-1474 |
| issn | 0008-543X 1097-0142 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5384867 |
| source | MEDLINE; Access via Wiley Online Library; EZB-FREE-00999 freely available EZB journals; Wiley Online Library (Open Access Collection); Alma/SFX Local Collection |
| subjects | Aged Aged, 80 and over Antibodies Antibodies, Viral - blood Antibodies, Viral - immunology Antigens Biomarkers Cancer Carcinoma, Merkel Cell - diagnosis Carcinoma, Merkel Cell - epidemiology Carcinoma, Merkel Cell - etiology Carcinoma, Merkel Cell - mortality Falling Female Health risks Humans Immunoglobulins Immunosuppression Male Merkel cell carcinoma (MCC) Merkel cell polyomavirus (MCPyV) Middle Aged Neoplasm Recurrence, Local Neoplasm Staging Oncogene Proteins, Viral - immunology Oncology oncoprotein Oncoproteins Patients Polyomaviridae Population Surveillance Prospective Studies Reproducibility of Results Risk Seroepidemiologic Studies serology Skin cancer T antigen Tumor markers Tumor Virus Infections - complications Tumor Virus Infections - immunology Tumor Virus Infections - virology |
| title | Viral oncoprotein antibodies as a marker for recurrence of Merkel cell carcinoma: A prospective validation study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-11T22%3A45%3A38IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Viral%20oncoprotein%20antibodies%20as%20a%20marker%20for%20recurrence%20of%20Merkel%20cell%20carcinoma:%20A%20prospective%20validation%20study&rft.jtitle=Cancer&rft.au=Paulson,%20Kelly%20G.&rft.date=2017-04-15&rft.volume=123&rft.issue=8&rft.spage=1464&rft.epage=1474&rft.pages=1464-1474&rft.issn=0008-543X&rft.eissn=1097-0142&rft_id=info:doi/10.1002/cncr.30475&rft_dat=%3Cproquest_pubme%3E1891874847%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1920469279&rft_id=info:pmid/27925665&rfr_iscdi=true |